Tricyclic Antidepressants (TCAs)

Psychiatric Drug Introduction

• Psychiatric medications can be broken down into the following categories
  • antidepressants
  • antipsychotics
  • bipolar medications
• anxiolytics

Overview

• Drugs
  • 3° TCAs
    • imipramine
    • amitriptyline
    • doxepin 
    • clomipramine
  • 2° TCAs
    • nortriptyline (most well tolerated)
    • desipramine (least histaminic)
    • protriptyline
• Mechanism
  • block reuptake of NE and serotonin
• Clinical use
  • major depression
  • enuresis (imipramine)
  • OCD (clomipramine)
  • fibromyalgia
  • painful diabetic neuropathy (amtitryptyline)
• Side effects
  • anticholinergic 
    • tachycardia, urinary retention, flushing, dry membranes, fever, mydriasis 
    • 3° TCAs worse than 2° TCAs
  • anti-histaminic
    • sedation
      • desipramine is the least sedating
  • ↓ seizure threshold
• Toxicity 
  • do NOT mix with SSRIs and MAOIs → can be fatal
  • 3 C’s of overdose 
    • Convulsions
    • Coma
    • Cardiotoxicity (arrhythmias) 
      • Brugada pattern (downsloping ST elevation with RBBB) 
  • respiratory depression, hyperpyrexia
  • confusion/hallucinations in the elderly
    • due to anticholinergic side effects
    • should use nortriptyline which has lesser SEs
  • Rx for overdose = NaHCO₃ 
    • sodium load treats CV toxicity (best answer for mechanism)
    • bicarbonate load could improve renal excretion and decrease TCA binding of sodium channels